ATP binding without hydrolysis switches sulfonylurea receptor 1 (SUR1) to outward-facing conformations that activate K channels.

Neuroendocrine-type ATP-sensitive K (K) channels are metabolite sensors coupling membrane potential with metabolism, thereby linking insulin secretion to plasma glucose levels. They are octameric complexes, (SUR1/Kir6.2), comprising sulfonylurea receptor 1 (SUR1 or ABCC8) and a K-selective inward rectifier (Kir6.

A brachytherapy photon radiation quality index Q(BT) for probe-type dosimetry.

Introduction: In photon brachytherapy (BT), experimental dosimetry is needed to verify treatment plans if planning algorithms neglect varying attenuation, absorption or scattering conditions. The detector's response is energy dependent, including the detector material to water dose ratio and the intrinsic mechanisms. The local mean photon energy E¯(r) must be known or another equivalent energy quality parameter used.

Reinterpreting the action of ATP analogs on K(ATP) channels.

Neuroendocrine-type K(ATP) channels, (SUR1/Kir6.2)4, couple the transmembrane flux of K(+), and thus membrane potential, with cellular metabolism in various cell types including insulin-secreting β-cells. Mutant channels with reduced activity are a cause of congenital hyperinsulinism, whereas hyperactive channels are a cause of neonatal diabetes.

Two neonatal diabetes mutations on transmembrane helix 15 of SUR1 increase affinity for ATP and ADP at nucleotide binding domain 2.

K(ATP) channels, (SUR1/Kir6.2)(4) (sulfonylurea receptor type 1/potassium inward rectifier type 6.2) respond to the metabolic state of pancreatic β-cells, modulating membrane potential and insulin exocytosis.

Role of the amino-terminal transmembrane domain of sulfonylurea receptor SUR2B for coupling to K(IR)6.2, ligand binding, and oligomerization.

ATP-sensitive K(+) (K(ATP)) channels consist of two types of subunits, K(IR)6.x that form the pore, and sulfonylurea receptors (SURs) that serve as regulatory subunits. SURs are ATP-binding cassette (ABC) proteins and contain, in addition to two nucleotide binding folds, the binding sites for channel openers such as diazoxide and P1075 and channel inhibitors such as glibenclamide (GBC) and repaglinide.

Importance of the Kir6.2 N-terminus for the interaction of glibenclamide and repaglinide with the pancreatic K(ATP) channel.

The pancreatic K(ATP) channel, SUR1/Kir6.2, couples insulin secretion to the plasma glucose level. The channel is an octamer with four Kir6.

Substitution of the Walker A lysine by arginine in the nucleotide-binding domains of sulphonylurea receptor SUR2B: effects on ligand binding and channel activity.

Sulphonylurea receptors (SURs) serve as regulatory subunits of ATP-sensitive K(+) channels. SURs are members of the ATP-binding cassette (ABC) protein superfamily and contain two conserved nucleotide-binding domains (NBDs) which bind and hydrolyse MgATP; in addition, they carry the binding sites for the sulphonylureas like glibenclamide (GBC) which close the channel and for the K(ATP) channel openers such as P1075. Here we have exchanged the conserved Lys in the Walker A motif by Arg in both NBDs of SUR2B, the regulatory subunit of the vascular K(ATP) channel.

Cyclic AMP increases cytoplasmic free calcium in renin-secreting cells from rat kidney.

The renin-secreting juxtaglomerular cells (JGC) in the media of the afferent arteriole at the vessel pole are the major source of circulating renin. The control of renin secretion is complex with increases in cAMP being the major stimulus and increases in intracellular free Ca2+ concentration ([Ca2+]i) being inhibitory. We measured [Ca2+]i in the afferent arteriole from mostly JGC.

Analysis of two KCNJ11 neonatal diabetes mutations, V59G and V59A, and the analogous KCNJ8 I60G substitution: differences between the channel subtypes formed with SUR1.

beta-Cell-type K(ATP) channels are octamers assembled from Kir6.2/KCNJ11 and SUR1/ABCC8. Adenine nucleotides play a major role in their regulation.

Effect of adenosine on membrane potential and Ca2+ in juxtaglomerular cells. Comparison with angiotensin II.

Background: Renin is mainly secreted from the juxtaglomerular cells (JGC) in the kidney situated in the afferent arteriole close to the vessel pole. Angiotensin II (ANG II) and adenosine inhibit renin secretion and synergistically constrict the afferent arteriole. ANG II depolarises JGC and increases the cytoplasmic free Ca2+ concentration [Ca2+]i.

Testing the bipartite model of the sulfonylurea receptor binding site: binding of A-, B-, and A + B-site ligands.

ATP-sensitive K(+) (K(ATP)) channels are composed of pore-forming subunits (Kir6.x) and of regulatory subunits, the sulfonylurea receptors (SURx). Subtypes of K(ATP) channels are expressed in different organs.

Whole body radiotherapy: A TBI-guideline.

Total Body Irradiation (TBI) is one main component in the interdisciplinary treatment of widely disseminated malignancies predominantly of haematopoietic diseases. Combined with intensive chemotherapy, TBI enables myeloablative high dose therapy and immuno-ablative conditioning treatment prior to subsequent transplantation of haematopoietic stem cells: bone marrow stem cells or peripheral blood progenitor stem cells. Jointly prepared by DEGRO and DGMP, the German Society of Radio-Oncology, and the German Association of Medical Physicists, this DEGRO/DGMP-Leitlinie Ganzkoerper-Strahlenbehandlung - DEGRO/DGMP Guideline Whole Body Radiotherapy, summarises the concepts, principles, facts and common methods of Total Body Irradiation and poses a set of recommendations for reliable and successful application of high dose large-field radiotherapy as essential part of this interdisciplinary, multi-modality treatment concept.

Lipids modulate ligand binding to sulphonylurea receptors.

ATP-sensitive K(+) channels (K(ATP) channels) are complexes of inwardly rectifying K(+) channels (Kir6.x) and sulphonylurea receptors (SURs). Kir6.

The mutation Y1206S increases the affinity of the sulphonylurea receptor SUR2A for glibenclamide and enhances the effects of coexpression with Kir6.2.

1. ATP-sensitive K(+) channels (K(ATP) channels) are tetradimeric complexes of inwardly rectifying K(+) channels (Kir6.x) and sulphonylurea receptors (SURs).

The impact of ATP-sensitive K+ channel subtype selectivity of insulin secretagogues for the coronary vasculature and the myocardium.

Insulin secretagogues (sulfonylureas and glinides) increase insulin secretion by closing the ATP-sensitive K+ channel (KATP channel) in the pancreatic beta-cell membrane. KATP channels subserve important functions also in the heart. First, KATP channels in coronary myocytes contribute to the control of coronary blood flow at rest and in hypoxia.

Electrophysiological and molecular characterization of the inward rectifier in juxtaglomerular cells from rat kidney.

Renin, the key element of the renin-angiotensin-aldosterone system, is mainly produced by and stored in the juxtaglomerular cells in the kidney. These cells are situated in the media of the afferent arteriole close to the vessel pole and can transform into smooth muscle cells and vice versa. In this study, the electrophysiological properties and the molecular identity of the K+ channels responsible for the resting membrane potential (approximately -60 mV) of the juxtaglomerular cells were examined.

Interaction of a novel dihydropyridine K+ channel opener, A-312110, with recombinant sulphonylurea receptors and KATP channels: comparison with the cyanoguanidine P1075.

1. ATP-sensitive K(+) channels (K(ATP) channels) are composed of pore-forming subunits (Kir6.x) and of regulatory subunits, the sulphonylurea receptors (SURx).

Virtual 3D IVUS vessel model for intravascular brachytherapy planning. I. 3D segmentation, reconstruction, and visualization of coronary artery architecture and orientation.

Intravascular brachytherapy (IVB) can significantly reduce the risk of restenosis after interventional treatment of stenotic arteries, if planned and applied correctly. To facilitate computer-based IVB planning, a three-dimensional vessel model has been derived from information on coronary artery segments acquired by intravascular ultrasound (IVUS) and biplane angiography. Part I describes the approach of model construction and presents possibilities of visualization.

Clinical beta radiation dosimetry for brachytherapy in terms of absorbed dose to water: ISO new work item proposal for international standardization.

Purpose: Beta radiation has found increasing interest in intravascular brachytherapy for successfully overcoming the severe problem of restenosis after interventional treatment of arterial stenosis. Prior to initiating procedures applying beta radiation there is a common need to specify methods for the determination and specification of the absorbed dose to water or tissue and their spatial distributions. The DIN-NAR standardization in radiology task group Dosimetry has initiated an international ad hoc working group for an ISO new work item proposal on the standardization of procedures in clinical beta radiation dosimetry.

Binding and effect of K ATP channel openers in the absence of Mg2+.

1 Openers of ATP-sensitive K(+) channels (K(ATP) channels) are thought to act by enhancing the ATPase activity of sulphonylurea receptors (SURs), the regulatory channel subunits. At higher concentrations, some openers activate K(ATP) channels also in the absence of MgATP. Here, we describe binding and effect of structurally diverse openers in the absence of Mg(2+) and presence of EDTA.

Dose finding in intracoronary brachytherapy--consequences from empirical trials.

In-stent restenosis has been shown to be associated with a high recurrence rate of repetitive restenosis and remains a challenging task in interventional cardiology. Randomized, placebo-controlled trials have established that beta- as well as gamma-based vascular brachytherapy reduces the incidence of restenosis and clinical event rates following percutaneous coronary intervention (PCI) for the treatment of in-stent restenosis with focal and moderate length. Despite the number of clinical trials with impressive and convincing data, dose finding in most trials is empirical and remains an open question in this fairly new field of percutaneous interventional procedures.

Mg2+ sensitizes KATP channels to inhibition by DIDS: dependence on the sulphonylurea receptor subunit.

1. ATP-sensitive potassium channels (K(ATP) channels) consist of pore-forming Kir6.x subunits and of sulphonylurea receptors (SURs).

The stereoenantiomers of a pinacidil analog open or close cloned ATP-sensitive K+ channels.

ATP-dependent K(+) channels (K(ATP) channels) are composed of pore-forming subunits Kir6.x and sulfonylurea receptors (SURs). Cyanoguanidines such as pinacidil and P1075 bind to SUR and enhance MgATP binding to and hydrolysis by SUR, thereby opening K(ATP) channels.

Glibenclamide binding to sulphonylurea receptor subtypes: dependence on adenine nucleotides.

1: ATP-sensitive K(+) channels are composed of pore-forming subunits Kir6.2 and of sulphonylurea receptors (SURs); the latter are the target of the hypoglycaemic sulphonylureas like glibenclamide. Here, we report on the negative allosteric modulation by MgATP and MgADP of glibenclamide binding to SUR1 and to SUR2 mutants with high glibenclamide affinity, SUR2A(Y1206S) and SUR2B(Y1206S).